Available evidence does not support the use of genotype-directed nutritional supplementation for patients at high risk of age related macular degeneration (AMD), according to findings from three separate statistical teams.
There has been considerable controversy in recent years regarding whether genotyping should be part of standard care for patients with age-related macular degeneration who are being considered for treatment with antioxidants and zinc.
Published in Ophthalmology, the study aimed to determine whether a patient’s genetic make-up predicted their response to supplements an AMD; ie, whether supplements had any impact on their progression to advanced AMD.
Three separate statistical teams reanalysed data derived from the Age-Related Eye Disease Study (AREDS), receiving data prepared by the AREDS investigators and, separately, data from investigators who reported findings that support the use of genotyping.
We found errors in the data used to support the initial claim of genotype-treatment interaction.
The teams looked at patients with AMD worse than category one, who were taking an AREDS supplement and had genotyping available. Data from the two groups overlapped imperfectly with respect to measurements made: the largest common set involved 879 participants who shared the same CFH and ARMS2 single nucleotide polymorphisms.
Each of the three statistical teams took a separate but complementary approach, with one focussing on data concordance between conflicting studies, the second replicated the key claim of an interaction between genotype and treatment, and the third took a blank slate approach in an attempt to find baseline predictors of treatment response.
The researchers reported that, “We found errors in the data used to support the initial claim of genotype-treatment interaction. Although we found evidence that high-risk patients had more to gain from treatment, we were unable to replicate any genotype–treatment interactions after adjusting for multiple testing. We tested one genotype claim on an independent set of data, with negative results. Even if we assumed that interactions in fact did exist, we did not find evidence to support the claim that supplementation leads to a large increase in the risk of advanced AMD in some genotype subgroups.”
They concluded, “Patients who meet criteria for supplements to prevent AMD progression should be offered zinc and antioxidants without consideration of genotype”.